Volume 47, Number 11, 1984-1989, DOI: 10.1007/s00125-004-1558-5

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European Association for the Study of Diabetes

IgG4-subclass of glutamic acid decarboxylase antibody is more frequent in latent autoimmune diabetes in adults than in type 1 diabetes

M. Hillman, C. Törn, H. Thorgeirsson and M. Landin-Olsson

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Abstract

Aims/hypothesis  

Glutamic acid decarboxylase autoantibodies (GADA) are the most frequent beta-cell-specific autoantibodies in type 1 diabetes and in latent autoimmune diabetes in adults (LADA). The autoimmune attack on pancreatic islet cells is associated with a T helper 1 cell (Th1) response, mainly represented by IgG1-subclass in humans. It has been proposed that the presence of IgG4 may be associated with a Th2 response. The aim of our study was to compare the GADA IgG-subclass distribution between adult patients with type 1 diabetes and LADA.

Methods  

Patients with type 1 diabetes (n=45) and patients with LADA (n=60) were included. Radioimmunoprecipitation assay with IgG-subclass specific Sepharose (IgG1, IgG2, IgG3 and IgG4) was used to precipitate the antibody/antigen-complex.

Results  

We only detected IgG4-subclass of GADA in subjects with LADA (26.7%; p<0.001). IgG1 was the most common GADA-subclass in both groups, however IgG1 as the solely expressed subclass was more common among type 1 diabetic patients (77.8%; p<0.05). The rank order of the frequencies of IgG-subclasses in type 1 diabetes was IgG1>IgG3>IgG2>IgG4 and in LADA patients IgG1>IgG4>IgG2>IgG3.

Conclusions/interpretation  

The difference in GADA IgG-subclasses could indicate a different immune response, possibly an altered balance between Th1 and Th2 cytokine profile in pancreatic islets. This difference could contribute to the slower rate of beta cell destruction in LADA patients, as reflected by a higher C-peptide level at clinical onset.

Keywords  Diabetes mellitus - GAD65 enzyme - Immunoglobulin G - Radioimmunoprecipitation assay

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